This program will provide a multifaceted approach to the study of the physiological significance of blood rheology studies. The long term goal of this application is to contribute to the understanding of the relation of the rheological properties of blood to the flow of blood in vivo, and the diagnosis and treatment of clinical disorders associated with potential rheological alterations. The specific aims of the program include: 1) studies aimed at defining the mechanisms of red blood cell aggregation induced bY water- soluble polymers and proteins, and the potential for affecting such aggregation via modification of the RBC surface; 2) a systematic exploration of RBC cellular factors which affect RBC aggregation, and thus the factors responsible for the much greater aggregation of old versus young RBC, and the wide range of aggregation observed washed RBCs from healthy adult donors; 3) continued studies with Dr. Paul Johnson (UCSD) to more fully define the effects of RBC aggregation on venous vascular resistance and to explore the usefulness of polymer-coated RBC in this in vivo system; 4) hemorheological evaluation of red cells and white cells from patients whose clinical state is characterized by altered rheological properties of blood (i.e. diabetes mellitis and hypertension). This research should provide: (1) greater insight into the process of RBC aggregation and the role of cellular factors versus suspending media properties, (2) quantitative information relevant to the effects of both decreased and enhanced RBC aggregation on blood flow and vascular resistance, and (3) detailed data regarding the macro- and micro-rheological properties of pathologic blood and the extent to which abnormalities can be normalized by appropriate treatment. The long range significance of these studies is their potential to contribute to clinical medicine, for example by increasing the understanding of the mechanisms that produce syndromes such as hyperviscosity.